tbuckley/cabot-search huggingface dataset:
P11.36.A TUMOR CONTROL AND FUNCTIONAL OUTCOME IN VESTIBULAR SCHWANNOMA - RESULTS FROM A DUAL-CENTER STUDY COMPARING MICROSURGERY AND GAMMA KNIFE RADIOSURGERY
Authors: S Wang, A Rick, F Ebner, A van Eck, G Naros, G Horstmann, M Tatagiba
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND The level of evidence to provide treatment recommendations for vestibular schwannoma (VS) is low. Both Stereotactic Radiosurgery (SRS) and microsurgical resection (SURG) are available as treatment options for VS. There are very few direct comparative studies comparing both treatment modalities in large cohorts allowing detailed subgroup analysis. MATERIAL AND METHODS This is a retrospective dual-center cohort study. Data was retrospectively collected from two large centers involved in the treatment of solitary vestibular schwannomas for patients between 2005 und 2011 to enable follow-up of up to 10 years. Tumor size was classified by Koos Classification. Clinical state was reported by House and Brackmann (H&amp;B) and Gardner-Robertson (G&amp;R) scale (with H&amp;B and G&amp;R 1-2 considered as good outcome), and Recurrence-free-survival (RFS) was assessed radiographically by contrast-enhanced MR imaging. VS-associated symptoms like trigeminal affection, tinnitus, and vertigo/imbalance were also collected. RESULTS The study population included N=901 patients, who were treated in both centers. N=559 patients were treated by SRS, and 342 patients by SURG.Treatment-related functional deterioration (e.g. hearing and facial deterioration) was significantly more common in patients treated by SURG. The incidence of complications was similar in both groups (14% and 13%). Secondary VS-related symptoms like tinnitus, vertigo, imbalance and trigeminal symptoms were significantly improved by microsurgery, but not by SRS. This study reported an overall incidence of recurrence in SURG of only 4%, and 11% in SRS respectively. Tumor control was comparable in small tumors (Koos I and II) in both SRS and SURG. Patients treated by SRS had significantly smaller tumors (p&amp;lt;0.001). In large VS (Koos III and IV), SURG is superior to SRS considering tumor control with a risk reduction for incidence of recurrence. CONCLUSION SRS can achieve similar tumor control compared to SURG in smaller VS (Koos I-II) - with less severe postinterventional morbidities (hearing and facial function loss). In large VS (Koos III-IV), tumor control by SRS is inferior to SURG. Therefore, while SURG is increasing the risk for facial palsy, it reduces the risk for recurrence. Moreover, SURG may improve secondary VS symptoms (e.g. tinnitus, vertigo/imbalance and trigeminal symptoms), even in small VS. Our data on tumor control and tumor size in SRS and SURG suggest that if combination therapy is chosen, the residual tumor for adjuvant SRS should not exceed the size of Koos II.These figures should be considered when deciding on treatment modality.
Bidirectional synaptic changes in deep and superficial hippocampal neurons following in vivo activity
Authors: Marcus Berndt, Massimo Trusel, Todd F. Roberts, Brad E. Pfeiffer, Lenora J. Volk
Journal: Neuron (2023)

Neuronal activity during experience is thought to induce plastic changes within the hippocampal network that underlie memory formation, although the extent and details of such changes in vivo remain unclear. Here, we employed a temporally precise marker of neuronal activity, CaMPARI2, to label active CA1 hippocampal neurons in vivo, followed by immediate acute slice preparation and electrophysiological quantification of synaptic properties. Recently active neurons in the superficial sublayer of stratum pyramidale displayed larger post-synaptic responses at excitatory synapses from area CA3, with no change in pre-synaptic release probability. In contrast, in vivo activity correlated with weaker pre- and post-synaptic excitatory weights onto pyramidal cells in the deep sublayer. In vivo activity of deep and superficial neurons within sharp-wave/ripples was bidirectionally changed across experience, consistent with the observed changes in synaptic weights. These findings reveal novel, fundamental mechanisms through which the hippocampal network is modified by experience to store information.
Imaging in inflammatory arthritis: progress towards precision medicine
Authors: Ioanna Minopoulou, Arnd Kleyer, Melek Yalcin-Mutlu, Filippo Fagni, Stefan Kemenes, Christian Schmidkonz, Armin Atzinger, Milena Pachowsky, Klaus Engel, Lukas Folle, Frank Roemer, Maximilian Waldner, Maria-Antonietta D'Agostino, Georg Schett, David Simon
Journal: Nature Reviews Rheumatology (2023)
Effects of Gestational Arsenic Exposures on Placental and Fetal Development in Mice: The Role of <i>Cyr61</i> m6A
Authors: Ya-Ping Song, Jin-Wei Lv, Zhi-Cheng Zhang, Qing-Hua Qian, Yi-Jun Fan, Dao-Zhen Chen, Heng Zhang, Fei-Xiang Xu, Cheng Zhang, Yichao Huang, Hua Wang, Wei Wei, De-Xiang Xu
Journal: Environmental Health Perspectives (2023)

Several epidemiological investigations demonstrated that maternal arsenic (As) exposure elevated risk of fetal growth restriction (FGR), but the mechanism remains unclear. This study aimed to investigate the effects of gestational As exposure on placental and fetal development and its underlying mechanism. Dams were exposed to 0.15, 1.5, and 15mg/L NaAsO2 throughout pregnancy via drinking water. Sizes of fetuses and placentas, placental histopathology, and glycogen content were measured. Placental RNA sequencing was conducted. Human trophoblasts were exposed to NaAsO2 (2μM) to establish an in vitro model of As exposure. The mRNA stability and protein level of genes identified through RNA sequencing were measured. N6-Methyladenosine (m6A) modification was detected by methylated RNA immunoprecipitation-quantitative real-time polymerase chain reason (qPCR). The binding ability of insulin-like growth factor 2 binding protein 2 to the gene of interest was detected by RNA-binding protein immunoprecipitation-qPCR. Intracellular S-adenosylmethionine (SAM) and methyltransferase activity were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and colorimetry, respectively. In vitro As+3 methyltransferase (As3MT) knockdown or SAM supplementation and in vivo folic acid (FA) supplementation were used to evaluate the protective effect. A case-control study verified the findings. Sizes of fetuses (exposed to 1.5 and 15mg/L NaAsO2) and placentas (exposed to 15mg/L NaAsO2) were lower in As-exposed mice. More glycogen+ trophoblasts accumulated and the expression of markers of interstitial invasion was lower in the 15mg/L NaAsO2-exposed mouse group in comparison with control. Placental RNA sequencing identified cysteine-rich angiogenic inducer 61 (Cyr61) as a candidate gene of interest. Mechanistically, mice and cells exposed to As had lower protein expression of CYR61, and this was attributed to a lower incidence of Cyr61 m6A. Furthermore, cells exposed to As had lower methyltransferase activity, suggesting that this could be the mechanism by which Cyr61 m6A was affected. Depletion of intracellular SAM, a cofactor for m6A methyltransferase catalytic domain, partially contributed to As-induced methyltransferase activity reduction. Either As3MT knockdown or SAM supplementation attenuated As-induced Cyr61 m6A down-regulation. In mice, FA supplementation rescued As-induced defective trophoblastic invasion and FGR. In humans, a negative correlation between maternal urinary As and plasma CYR61 was observed in infants who were small for gestational age. Using in vitro and in vivo models, we found that intracellular SAM depletion-mediated Cyr61 m6A down-regulation partially contributed to As-induced defective trophoblastic invasion and FGR. https://doi.org/10.1289/EHP12207.
The Effect of Individual or Study-Wide Report-Back on Knowledge, Concern, and Exposure-Reducing Behaviors Related to Endocrine-Disrupting Chemicals
Authors: Katherine E. Boronow, Barbara Cohn, Laurie Havas, Marj Plumb, Julia Green Brody
Journal: Environmental Health Perspectives (2023)

To make informed decisions about endocrine-disrupting chemicals (EDCs), people need functional understanding of exposures and health and an ability to act on their knowledge. The return of biomonitoring results is an opportunity to educate people about EDCs and motivate exposure reduction.This study investigates environmental health knowledge about EDCs, concerns about health effects, and exposure-reducing behaviors before and after the return of individual-level exposure results or only study-wide results.Women in the Child Health and Development Studies who were biomonitored for 42 EDCs were randomly assigned to receive a report with personal chemical results or only study-wide findings. We interviewed participants before and after report-back about their knowledge and concerns about EDCs and how frequently they performed exposure-related behaviors. We investigated baseline differences by education and race and examined changes after report-back by race and report type.Participants (n=135) demonstrated general understanding of exposure pathways and health impacts of EDCs. For 9 out of 20 knowledge questions, more than 90% of participants (n≥124) gave correct responses at baseline, including for questions about chemicals' persistence in the body and effects of early-life exposure. Most participants held two misconceptions-about chemical safety testing in the United States and what doctors can infer from EDC results-although errors decreased after report-back. Initially, concern was higher for legacy pollutants, but report-back increased concern for consumer product chemicals. After report-back, participants took some actions to reduce exposures, particularly to per- and polyfluoroalkyl substances, and total behavior was associated with knowledge and concern but not race, education, or report type.This study demonstrated that participants had foundational knowledge about EDCs and that report-back further built their environmental health literacy. We conclude that future communications should target misconceptions about chemicals regulation in the United States, because information about regulations is crucial for people to evaluate risks posed by consumer product chemicals and decide whether to engage with public policy. https://doi.org/10.1289/EHP12565.
Nephron Sparing Treatment (NEST) for Small Renal Masses: A Feasibility Cohort-embedded Randomised Controlled Trial Comparing Percutaneous Cryoablation and Robot-assisted Partial Nephrectomy
Authors: Joana B. Neves, Hannah Warren, Joseph Santiapillai, Nicola Rode, David Cullen, Menelaos Pavlou, Miles Walkden, Prasad Patki, Ravi Barod, Faiz Mumtaz, Michael Aitchison, Steven Bandula, Elena Pizzo, Veronica Ranieri, Norman Williams, William Wildgoose, Kurinchi Gurusamy, Mark Emberton, Axel Bex, Maxine G.B. Tran
Journal: European Urology (2023)

There is a paucity of high-level evidence on small renal mass (SRM) management, as previous classical randomised controlled trials (RCTs) failed to meet accrual targets. Our objective was to assess the feasibility of recruitment to a cohort-embedded RCT comparing cryoablation (CRA) to robotic partial nephrectomy (RPN). A total of 200 participants were recruited to the cohort, of whom 50 were enrolled in the RCT. In the RCA intervention arm, 84% consented (95% confidence interval [CI] 64–95%) and 76% (95% CI 55–91%) received CRA; 100% (95% CI 86–100%) of the control arm underwent RPN. The retention rate was 90% (95% CI 79–96%) at 6 mo. In the RPN group 2/25 (8%) were converted intra-operative to radical nephrectomy. Postoperative complications (Clavien-Dindo grade 1–2) occurred in 12% of the CRA group and 29% of the RPN group. The median length of hospital stay was shorter for CRA (1 vs 2 d; p = 0.019). At 6 mo, the mean change in renal function was −5.0 ml/min/1.73 m2 after CRA and −5.8 ml/min/1.73 m2 after RPN. This study demonstrates the feasibility of a cohort-embedded RCT comparing CRA and RPN. These data can be used to inform multicentre trials on SRM management. We assessed whether patients with a small kidney tumour would consent to a trial comparing two different treatments: cryoablation (passing small needles through the skin to freeze the kidney tumour) and surgery to remove part of the kidney. We found that most patients agreed and a full trial would therefore be feasible.
Efficacy and safety of upadacitinib maintenance therapy for moderately to severely active ulcerative colitis in patients responding to 8 week induction therapy (U-ACHIEVE Maintenance): overall results from the randomised, placebo-controlled, double-blind, phase 3 maintenance study
Authors: Séverine Vermeire, Silvio Danese, Wen Zhou, Dapo Ilo, Justin Klaff, Gweneth Levy, Xuan Yao, Su Chen, Yuri Sanchez Gonzalez, Xavier Hébuterne, James O Lindsay, Peter D R Higgins, Qian Cao, Hiroshi Nakase, Jean-Frédéric Colombel, Edward V Loftus, Remo Panaccione
Journal: The Lancet. Gastroenterology & hepatology (2023)
Genitourinary cancer neoadjuvant therapies: current and future approaches
Authors: Sujit S. Nair, Dimple Chakravarty, Vaibhav Patel, Nina Bhardwaj, Ashutosh K. Tewari
Journal: Trends in cancer (2023)

Neoadjuvant therapies can improve tolerability, reduce tumor volume to facilitate surgery, and assess subsequent treatment response. Therefore, there is much enthusiasm for expanding the benefits of cancer therapies to the neoadjuvant setting to reduce recurrence and improve survival in patients with localized or locally advanced genitourinary (GU) cancer. This approach is clinically pertinent because these treatments are administered primarily to treatment-naive patients and can elicit the greatest drug response. In addition, the results are not impacted by other anticancer treatments. While neoadjuvant therapies have been the standard treatment for bladder cancer in the past, they are presently restricted to clinical trials for renal and prostate cancer (PCa); however, changes are imminent. Precision neoadjuvant therapies will be ushered in by biomarker-stratified neoadjuvant trials with appropriate survival endpoints and comprehensive correlative and imaging studies. This review discusses neoadjuvant studies in GU malignancies and how they inform future study design considerations.
An additive-free multifunctional β-glucan-peptide hydrogel participates in the whole process of bacterial-infected wound healing
Authors: Li Li, Yinglu Wang, Zhengjun Huang, Zuxian Xu, Ruipin Cao, Jiaxin Li, Biyi Wu, Jian Ren Lu, Hu Zhu
Journal: Journal of Controlled Release (2023)
Development of AAV-delivered broadly neutralizing anti-human ACE2 antibodies against SARS-CoV-2 variants
Authors: Cheng-Pu Sun, Chi-Wen Chiu, Ping-Yi Wu, Szu-I Tsung, I-Jung Lee, Chih-Wei Hu, Min-Feng Hsu, Tzu-Jiun Kuo, Yu-Hua Lan, Li-Yao Chen, Hui-Yee Ng, Meng-Jhe Chung, Hsin-Ni Liao, Sheng-Che Tseng, Chia-Hui Lo, Yung-Jiun Chen, Chun-Che Liao, Chih-Shin Chang, Jian-Jong Liang, Piotr Draczkowski, Sarita Puri, Yuan-Chih Chang, Jing-Siou Huang, Cheng-Cheung Chen, Jyh-Hwa Kau, Yen-Hui Chen, Wen-Chun Liu, Han-Chung Wu, Shang-Te Danny Hsu, I-Hsuan Wang, Mi-Hua Tao
Journal: Molecular Therapy (2023)

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the emergence of new variants that are resistant to existing vaccines and therapeutic antibodies, has raised the need for novel strategies to combat the persistent global COVID-19 epidemic. In this study, a monoclonal anti-human angiotensin-converting enzyme 2 (hACE2) antibody, ch2H2, was isolated and humanized to block the viral receptor-binding domain (RBD) binding to hACE2, the major entry receptor of SARS-CoV-2. This antibody targets the RBD-binding site on the N terminus of hACE2 and has a high binding affinity to outcompete the RBD. In vitro, ch2H2 antibody showed potent inhibitory activity against multiple SARS-CoV-2 variants, including the most antigenically drifted and immune-evading variant Omicron. In vivo, adeno-associated virus (AAV)-mediated delivery enabled a sustained expression of monoclonal antibody (mAb) ch2H2, generating a high concentration of antibodies in mice. A single administration of AAV-delivered mAb ch2H2 significantly reduced viral RNA load and infectious virions and mitigated pulmonary pathological changes in mice challenged with SARS-CoV-2 Omicron BA.5 subvariant. Collectively, the results suggest that AAV-delivered hACE2-blocking antibody provides a promising approach for developing broad-spectrum antivirals against SARS-CoV-2 and potentially other hACE2-dependent pathogens that may emerge in the future.
Advancing the pipeline of cystic fibrosis clinical trials: a new roadmap with a global trial network perspective
Authors: Nicole Mayer-Hamblett, John Paul Clancy, Raksha Jain, Scott H Donaldson, Isabelle Fajac, Christopher H Goss, Deepika Polineni, Felix Ratjen, Bradley S Quon, Edith T Zemanick, Scott C Bell, Jane C Davies, Manu Jain, Michael W Konstan, Natanya R Kerper, Tré LaRosa, Marcus A Mall, Edward McKone, Kelsie Pearson, Joseph M Pilewski, Lynne Quittell, Jonathan H Rayment, Steven M Rowe, Jennifer L Taylor-Cousar, George Retsch-Bogart, Damian G Downey
Journal: The Lancet Respiratory Medicine (2023)
Biofabrication methods for reconstructing extracellular matrix mimetics
Authors: Abdellah Aazmi, Duo Zhang, Corrado Mazzaglia, Mengfei Yu, Zhen Wang, Huayong Yang, Yan Yan Shery Huang, Liang Ma
Journal: Bioactive Materials (2023)

In the human body, almost all cells interact with extracellular matrices (ECMs), which have tissue and organ-specific compositions and architectures. These ECMs not only function as cellular scaffolds, providing structural support, but also play a crucial role in dynamically regulating various cellular functions. This comprehensive review delves into the examination of biofabrication strategies used to develop bioactive materials that accurately mimic one or more biophysical and biochemical properties of ECMs. We discuss the potential integration of these ECM-mimics into a range of physiological and pathological in vitro models, enhancing our understanding of cellular behavior and tissue organization. Lastly, we propose future research directions for ECM-mimics in the context of tissue engineering and organ-on-a-chip applications, offering potential advancements in therapeutic approaches and improved patient outcomes.
Functional regeneration at the blood-biomaterial interface
Authors: Dina M. Ibrahim, Aleksandra Fomina, Carlijn V.C. Bouten, Anthal I.P.M. Smits
Journal: Advanced Drug Delivery Reviews (2023)

The use of cardiovascular implants is commonplace in clinical practice. However, reproducing the key bioactive and adaptive properties of native cardiovascular tissues with an artificial replacement is highly challenging. Exciting new treatment strategies are under development to regenerate (parts of) cardiovascular tissues directly in situ using immunomodulatory biomaterials. Direct exposure to the bloodstream and hemodynamic loads is a particular challenge, given the risk of thrombosis and adverse remodeling that it brings. However, the blood is also a source of (immune) cells and proteins that dominantly contribute to functional tissue regeneration. This review explores the potential of the blood as a source for the complete or partial in situ regeneration of cardiovascular tissues, with a particular focus on the endothelium, being the natural blood-tissue barrier. We pinpoint the current scientific challenges to enable rational engineering and testing of blood-contacting implants to leverage the regenerative potential of the blood.
Real-time crash risk forecasting using Artificial-Intelligence based video analytics: A unified framework of generalised extreme value theory and autoregressive integrated moving average model
Authors: Fizza Hussain, Yasir Ali, Yuefeng Li, Md Mazharul Haque
Journal: Analytic Methods in Accident Research (2023)

With the recent advancements in computer vision and artificial intelligence, traffic conflicts occurring at an intersection and associated traffic characteristics can be obtained at the granular level of a signal cycle in real-time. This capability enables the estimation of the real-time crash risk using sophisticated modelling techniques, e.g., extreme value theory. However, these models are inherently incapable of forecasting the crash risk of future time periods based on the temporal dependency of crash risks. This study proposes a unified framework of extreme value theory and autoregressive integrated moving average models for forecasting crash risks at signalised intersections. At the first level of this framework, a non-stationary generalised extreme value model has been developed to estimate the real-time rear-end crash risk at the signal cycle level using the video data collected from three signalised intersections in Queensland, Australia. To capture the time-varying effect of different traffic conditions on conflict extremes, traffic flow, speed, shockwave area, and platoon ratio covariates are incorporated into the generalised extreme value model. The signal cycle-level crash risks obtained from the first level form a univariate time series, which is modelled using two variants of autoregressive integrated moving average model to forecast the crash risk of future signal cycles. Results reveal that the autoregressive integrated moving average model with exogenous variables outperforms the model without exogenous variables and can forecast the crash risk for the next 30-35 minutes with reasonable accuracy. Similarly, results also demonstrate that different crash risk patterns within a typical day are accurately predicted. The proposed framework helps identify the spatiotemporal windows where safety gradually deteriorates over time, thus enabling proactive safety assessment.
Single-cell RNA-sequencing reveals heterogeneity and intercellular crosstalk in human tuberculosis lung
Authors: Lin Wang, Hui Ma, Zilu Wen, Liangfei Niu, Xinchun Chen, Haiying Liu, Shulin Zhang, Jianqing Xu, Yijun Zhu, Hongwei Li, Hui Chen, Lei Shi, Laiyi Wan, Leilei Li, Meiyi Li, Ka-Wing Wong, Yanzheng Song
Journal: Journal of Infection (2023)

Lung inflammation indicated by 18F-labeled fluorodeoxyglucose (FDG) in patients with tuberculosis is associated with disease severity and relapse risk upon treatment completion. We revealed the heterogeneity and intercellular crosstalk in lung tissues with 18F-FDG avidity and adjacent uninvolved tissues from 6 tuberculosis patients by single-cell RNA-sequencing. Tuberculous lungs had an influx of regulatory T cells (Treg), exhausted CD8 T cells, immunosuppressive myeloid cells, conventional DC, plasmacytoid DC, and neutrophils. Immune cells in inflamed lungs showed general up-regulation of ATP synthesis and interferon-mediated signaling. Immunosuppressive myeloid and Treg cells strongly displayed transcriptions of genes related to tuberculosis disease progression. Intensive crosstalk between IL4I1-expressing myeloid cells and Treg cells involving chemokines, costimulatory molecules, and immune checkpoints, some of which being specific in 18F-FDG-avid lungs, were found. Our analysis provides insights into the transcriptomic heterogeneity and cellular crosstalk in pulmonary tuberculosis and guide unveiling cellular and molecular targets for tuberculosis therapy.